small microscope

Pearls from International EDS conference in Rome, Italy

I had the privilege and opportunity to attend the international EDS conference in Rome, Italy, in September 2022. The following are updates on several topics that I felt would be useful or of interest to the EDS community.

LDN and hEDS

A study conducted by the Comprehensive Center for Spine Care at Cornell University in New York, evaluated 136 patients from 2018 through 2021 and found that low-dose naltrexone was safe and potentially effective therapeutic for hEDS patients with chronic pain and mood disturbance. Interestingly, however, they found the MED or maximally effective dose quite variable in patients ranging from 0.1-5.2 mg per day suggesting that alterations to the current titrating dosing of 1.5 mg, 3.0 mg, and 4.5 mg administered over several weeks may be needed. 

Piezogenic Papules - not so unusual after all

Piezogenic pedal papules (PPP) develop from herniation of subcutaneous fat into the dermis, creating fleshy, often yellow colored “bumps”  on the heels of the feet. Their presence in a patient being evaluated for hEDS meets a systemic connective tissue finding as per the March 2017 modified criteria for diagnosis.

A study out of the University of Toronto evaluated both hEDS/HSD and non-EDS patients and found that the prevalence of PPP was similar in HSD and non-EDS patients (47.3% versus 45%). Although the prevalence of PPP was higher in hEDS patients versus non-EDS individuals the positive predictive value of PPP to diagnose hEDS was deemed to be poor. 

They concluded that PPP are a normal finding and not specific to EDS, stating that it is unlikely that they develop from weak collagen and were not associated with hypermobility or features of skin fragility.

Update on hEDS Genetics - from MUSC and Dr. Norris

EDS is a group of heritable connective tissue disorders resulting in the general features of joint hypermobility and tissue fragility. The initial genetic findings revealed mutations in collagen genes or genes involved in collagen synthesis or processing. Although the genetic basis for most subtypes of EDS are well characterized, very little is known about the underlying Genetics and biology of hEDS. 

It is postulated that the variability in severity and presentation in hEDS patients is linked to a multitude of genetic changes or more simply, that changes in a number of different genes are linked to and causative of hEDS.

Dr. Norris’ lab at MUSC recently identified a candidate gene, Gene X G226D, from a multigenerational family with hEDS and has used this information to generate a genetically and phenotypically accurate mouse model that enables them to study mechanisms of disease pathogenesis. Protein studies suggest that this gene may be linked to extracellular matrix dysfunction in hEDS.

In order to better understand the prevalence of this pathogenic variant (mutation) and to identify additional variants, they completed whole exome sequencing on 250 individuals with an hEDS diagnosis. These studies identified additional gene candidates currently undergoing investigation. 

And For the Kids

To address concerns regarding an increased fracture risk among children with EDS a group at Sick Kids in Toronto looked at 30 children with EDS, 6 of whom had hEDS and and 60 cases of GJH or generalized joint hypermobility.

The researchers found that the fracture prevalence in the EDS population was 26.7% (8/30). Two of the six patients with hEDS had fractures, none occurring before two years of age. In the GJH group, fracture prevalence was 25% parentheses (15/60) and no fractures occurred younger than 17 months of age. In both groups, all fractures occurred in the limbs with the exception of several fractures associated with clear traumatic injury to other parts of the body as could occur in a motor vehicle accident, for example. 

Overall, this data supports increased fracture risk for EDS and GJH pediatric patients. While the reasoning is unclear, I postulate that increased falling among young children with possible abnormal torque placed on limb bones due to hypermobility may lead to increased fracture risk. 


Fran D. Kendall, M.D.

This post is not meant to be a recommendation or a substitute for professional advice and services rendered by qualified doctors, allied medical personnel, and other professional services. The responsibility for any use of this information, or for proper medical treatment, rests with you.